Isatuximab for Monoclonal Gammopathy

Recruiting at 2 trial locations

Overseen By Research Nurse Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Columbia University

Must not be taking: CD38 antibodies, Rituximab

Disqualifiers: Multiple myeloma, B cell lymphoma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 0

Duration: 6 months

27 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to see whether Isatuximab can help improve kidney function of participants with MGRS. Isatuximab is approved by the Food and Drug Administration (FDA) for the treatment of adult patients with multiple myeloma, but it is not approved by the FDA to treat MGRS. This means that the use of isatuximab in this study is considered 'investigational'.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but there is a required 'washout' period (time without taking certain medications) of 12 weeks for chemotherapy-based therapies and 24 weeks for Rituximab-based therapies before starting the trial.

Is isatuximab safe for human use?

Isatuximab has been generally well tolerated in clinical trials for multiple myeloma, with common side effects including mild to moderate infusion reactions. No new safety concerns have been identified, and it has an acceptable safety profile when used alone or in combination with other treatments. ^{1 2 3 4 5}

How is the drug Isatuximab unique for treating monoclonal gammopathy?

Isatuximab is unique because it is a monoclonal antibody that specifically targets the CD38 protein on abnormal cells, which is different from other treatments that may not target this protein. It is administered intravenously and is often combined with other drugs like pomalidomide and dexamethasone to enhance its effectiveness, especially in patients with multiple myeloma who have not responded to previous treatments. ^{1 3 6 7 8}

Research Team

Divaya Bhutani, MD

Principal Investigator

Assistant Professor of Medicine at the Columbia University

Eligibility Criteria

Adults over 18 with MGRS, a kidney condition linked to abnormal proteins in the blood. They should have a life expectancy over 6 months, be relatively active (ECOG ≤2), and have normal organ/marrow function. Those previously treated for MGRS can join if they haven't used CD38 antibody therapy or had certain treatments within the last 3-6 months.

Inclusion Criteria

I have a kidney condition diagnosed through a biopsy, related to abnormal protein deposits.

Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2.

total bilirubin within normal institutional limits

Exclusion Criteria

I have been diagnosed with Multiple Myeloma, high-risk smoldering Multiple Myeloma, or a B cell lymphoma that requires treatment.

Participants who are receiving any other investigational agents concurrently.

I haven't had chemotherapy in the last 12 weeks or Rituximab in the last 24 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive Isatuximab for 6 months

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Isatuximab

Trial Overview The trial is testing Isatuximab's effectiveness on improving kidney function in MGRS patients. Although FDA-approved for multiple myeloma, its use here is investigational as it's not yet approved for treating MGRS.

Participant Groups

Group I: Isatuximab for MGRS Experimental Treatment 1 Intervention

Subjects will receive Isatuximab for 6 months and will be followed for an additional one year post therapy for outcome follow-up.

Isatuximab is already approved in European Union, United States for the following indications:

Approved in European Union as Sarclisa for:

• Multiple myeloma

Approved in United States as Sarclisa for:

• Multiple myeloma in combination with pomalidomide and dexamethasone for adults who have received at least two prior therapies including lenalidomide and a proteasome inhibitor
• Multiple myeloma in combination with carfilzomib and dexamethasone for adults with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
• Newly diagnosed multiple myeloma in combination with bortezomib, lenalidomide, and dexamethasone for adults who are not eligible for autologous stem cell transplant

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Genzyme, a Sanofi Company

Industry Sponsor

Trials

528

Recruited

186,000+

David Meeker

Genzyme, a Sanofi Company

Chief Executive Officer since 2011

MD from the University of Vermont Medical School, Advanced Management Program at Harvard Business School

Jean-Paul Kress

Genzyme, a Sanofi Company

Chief Medical Officer since 2015

MD from Faculte Necker-Enfants Malades, Paris

Findings from Research

Isatuximab is an IgG1 monoclonal antibody that targets CD38 on cancer cells and has been approved in the USA for treating multiple myeloma in patients who have undergone at least two prior therapies.

The approval of isatuximab, in combination with pomalidomide and dexamethasone, marks a significant advancement in treatment options for adult patients with relapsed and refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab: First Approval. Dhillon, S.[2021]

Isatuximab, an anti-CD38 monoclonal antibody, was found to be well tolerated and effective in treating heavily pretreated relapsed/refractory multiple myeloma, with an overall response rate of 36.4% in a phase 2 trial involving 28 patients.

The most common side effects were mild infusion reactions occurring in 42.9% of patients, indicating a manageable safety profile, while the median progression-free survival was 4.7 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab monotherapy in relapsed/refractory multiple myeloma: A Japanese, multicenter, phase 1/2, safety and efficacy study. Sunami, K., Suzuki, K., Ri, M., et al.[2020]

Isatuximab, an anti-CD38 monoclonal antibody, significantly improves progression-free survival and tumor response when combined with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma, based on phase III studies.

The combination therapies involving isatuximab were generally well tolerated, maintaining health-related quality of life and showing a manageable safety profile without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab: A Review of Its Use in Multiple Myeloma. Frampton, JE.[2022]

In a Phase 3 trial with 302 patients suffering from relapsed/refractory multiple myeloma, the combination of isatuximab with carfilzomib-dexamethasone significantly prolonged progression-free survival (PFS) to a median of 35.7 months compared to 19.2 months for carfilzomib-dexamethasone alone.

The addition of isatuximab also resulted in higher rates of complete response (44.1% vs 28.5%) and minimal residual disease negativity (33.5% vs 15.4%), indicating improved efficacy without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study. Martin, T., Dimopoulos, MA., Mikhael, J., et al.[2023]

Isatuximab monotherapy was found to be well tolerated and effective in Japanese patients with relapsed/refractory multiple myeloma, with an overall response rate of 36.4% and a clinical benefit rate of 54.5%.

The study identified a recommended dose of 20 mg/kg administered weekly and bi-weekly, with a median progression-free survival of 5.6 months, indicating promising antitumor activity and an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD38 antibody isatuximab monotherapy for Japanese individuals with relapsed/refractory multiple myeloma: An update of the phase 1/2 ISLANDs study. Sunami, K., Fuchida, SI., Suzuki, K., et al.[2023]

Isatuximab, a monoclonal antibody targeting CD38, was shown to significantly improve progression-free survival in adult patients with relapsed and refractory multiple myeloma when used in combination with pomalidomide and dexamethasone, compared to pomalidomide plus dexamethasone alone.

While treatment with isatuximab was associated with a higher incidence of treatment-related adverse events, including serious complications, the overall safety profile was deemed acceptable, leading to a positive benefit-risk ratio for its use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Isatuximab in Combination with Pomalidomide and Dexamethasone for the Treatment of Adult Patients with Relapsed and Refractory Multiple Myeloma. Delgado, J., Zienowicz, M., van Hennik, PB., et al.[2021]

Isatuximab, a monoclonal antibody targeting CD38, has been studied in 476 multiple myeloma patients and shows a two-compartment pharmacokinetic model, indicating its complex behavior in the body, especially in patients with different types of immunoglobulin.

Patients with IgG M-protein had lower drug exposure, but no dose adjustments were necessary as the efficacy and safety profiles remained consistent across different immunoglobulin types, suggesting that isatuximab's effectiveness is robust regardless of the patient's specific disease characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-Disease Interaction and Time-Dependent Population Pharmacokinetics of Isatuximab in Relapsed/Refractory Multiple Myeloma Patients. Fau, JB., El-Cheikh, R., Brillac, C., et al.[2023]

In a phase 3 study involving 307 patients with relapsed and refractory multiple myeloma, the combination of isatuximab, pomalidomide, and dexamethasone significantly improved progression-free survival (11.5 months) compared to pomalidomide and dexamethasone alone (6.5 months).

The most common side effects included infusion reactions and upper respiratory infections, with a low incidence of treatment-related deaths, indicating that isatuximab is a relatively safe and effective treatment option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Attal, M., Richardson, PG., Rajkumar, SV., et al.[2020]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Isatuximab: First Approval. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Isatuximab monotherapy in relapsed/refractory multiple myeloma: A Japanese, multicenter, phase 1/2, safety and efficacy study. [2020]

3. France pubmed.ncbi.nlm.nih.gov

Isatuximab: A Review of Its Use in Multiple Myeloma. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Anti-CD38 antibody isatuximab monotherapy for Japanese individuals with relapsed/refractory multiple myeloma: An update of the phase 1/2 ISLANDs study. [2023]

6. England pubmed.ncbi.nlm.nih.gov

EMA Review of Isatuximab in Combination with Pomalidomide and Dexamethasone for the Treatment of Adult Patients with Relapsed and Refractory Multiple Myeloma. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Drug-Disease Interaction and Time-Dependent Population Pharmacokinetics of Isatuximab in Relapsed/Refractory Multiple Myeloma Patients. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. [2020]